US 2006/0235670 A1 · Method and system for selecting therapeutic targets using molecular interaction dynamic networks

Abstract

The present invention concerns the field of integrative analysis of molecular interactions in a biological system. In particular, it pertains to a method for obtaining a dynamic model of a molecular interaction network in a biological system that allows analysis of said interactions when a stimulus is applied to the dynamic model, with a view in particular of hierarchizing biological molecules or selecting therapeutic targets in respect of a given biological problem, in particular to define a therapeutic action to be applied to said molecules. The invention also pertains to an informatics system for producing a dynamic model of a molecular interaction network in a biological system, and analyzing said molecular interactions when a stimulus is applied to the dynamic model, the informatics system comprising at least one central data processing unit connected to at least one quantitative experimental database.

Claims39

Dependent claims

A method for producing a dynamic model of a molecular interaction network in a biological system, allowing analysis of said network of interactions when a stimulus is applied to the dynamic model, in order to hierarchize biological molecules or select therapeutic targets in respect of a given biological problem, in particular to define- a therapeutic action to be applied to said molecules, said method being implemented by an informatics system and comprising the following steps:

A) from a static graph the vertices of which represent biological molecules and the arcs of which represent physico-chemical interactions existing between said molecules, associating an experimentally measured quantitative variable Xi with each vertex i, and a mathematical relationship with each arc of the graph, each of said relationships having the following characteristics:
it comprises an inertial term (i) which tends towards a finite limit;
it comprises a term (ii) tending to cause the variables Xi to return to their initial state, of opposite sign to the inertial term (i), and for which the variation as a fimction of time increases in absolute value more slowly than the variation as a ftnction of time of the inertial term (i);
it comprises a weighting factor wij which can take account of the combination of effects which may be exerted on each vertex of the graph;
B) computing the parameters of each relationship from quantitative experimental data concerning the vertices of the graph, by carrying out gradient descent learning techniques used for network parameterization.

2 more elements

A method for analyzing a molecular interaction network in a biological system by implementing an informatics system, comprising the following steps:

A′) using a dynamic model of a molecular interaction network, said model being constructed from a static graph the vertices of which represent biological molecules of the biological system and the edges of which represent physico-chemical interactions between said molecules, and from experimental data concerning the amounts or activities of said biological molecules and susceptible of being obtained by a method according to
C) a graph state, measured experimentally, is selected as the “state to be modified” and the duration of the biological process to be stimulated is defined and cut into a series of time steps;
D) a plurality of iterative simulation procedures are carried out, each comprising the following steps:
a) a stimulus is imposed on the state to be modified, i.e. the value of one or more quantitative variables associated with the vertices of the graph is modified, thus constituting a starting state for the simulation;
b) from the starting state of the simulation, a propagation computation is carried out within the graph.

2 more elements

Dependencies are inferred from the claim text.

Method and system for selecting therapeutic targets using molecular interaction dynamic networks

Life of this patent

Method and system for selecting therapeutic targets using molecular interaction dynamic networks

Life of this patent

Abstract

Claims39